1. Field of the Invention
This invention relates to the transdermal delivery of drugs. More specifically, a transdermal drug delivery system is utilized to deliver a therapeutically effective amount of a drug, via a modulated drug delivery profile, through the skin of a patient in need of such treatment. This device is particularly suitable for the delivery of tolerance-inducing drugs.
2. Description of the Background Art
Delivery of drugs by the transdermal route has been known to be theoretically possible for many years. The earliest patented transdermal devices were medicated bandages, usually with the drug mixed into the adhesive, that were designed to deliver a specific quantity of drug to a defined area of skin for a specific time. Such devices usually did not control the rate at which the drug was released. Since the 1970's interest in using the transdermal route for controlled release therapy has grown substantially.
Controlled release transdermal devices rely for their effect on the delivery of a known flux of drug to the skin for a prolonged period of time, generally a day, several days, or a week. The patch design influences and, to a certain extent, regulates the flux of drug. In one standard patch design, the drug is contained in a reservoir, with one or more layers separating the reservoir from the skin of the wearer. Typically, these layers are a synthetic membrane and an adhesive. The drug diffuses through these layers to the skin. In another common patch design, the drug is dissolved or suspended in a polymer or adhesive matrix which is in direct contact with the skin of the wearer. In this case, the drug diffuses from the matrix into the skin.
The skin is an effective barrier against the majority of drugs. Unless the delivery device is made unacceptably large, or the natural skin permeation rate of the drug is somehow increased by the use of enhancers, then the drug flux across the skin is generally inadequate for useful therapy. Thus, although in theory any drug might be delivered by this route, serious investigation of candidate drugs has been limited to those few that exhibit suitable properties, namely: small molecular size; short half-life; extensive and rapid liver metabolization, thus rendering oral administration difficult; high in vivo skin permeability; and small effective therapeutic dose, etc.
The delivery of drugs through the skin provides many advantages; primarily, such a means of delivery is a comfortable, convenient and noninvasive way of administering drugs. The variable rates of absorption and metabolism encountered in oral treatment are avoided, and other inherent inconveniences, e.g., gastrointestinal irritation and the like, are eliminated as well. Transdermal drug delivery also makes possible a high degree of control over blood concentrations of any particular drug.
The vast majority of transdermal systems are designed so as to deliver a drug continuously throughout the wearing period. For many drugs, however, continuous delivery poses the potential problem of tolerance. For such drugs, a continuous delivery patch must be removed periodically during the wearing period so as to prevent development of tolerance. The inconvenience of periodic patch removal can in turn create problems with patient compliance and thus with drug efficacy as well.
To date, it has been difficult to transdermally deliver tolerance-inducing drugs in therapeutically effective profiles. It is therefore desirable to provide improved devices and approaches which avoid the disadvantages of these conventional devices and methods while providing an effective means for delivering tolerance-inducing drugs.